Darbepoetin alpha for the treatment of anemia in patients with myelodysplastic syndromes.

Background: Anemia occurs as a comorbidity in from 80% to 85% of patients with myelodysplastic syndromes (MDS): It causes fatigue, increases transfusion needs, and reduces quality of life. Darbepoetin alpha (DA) is an erythropoiesis-stimulating protein (ESP) that is more highly glycosylated and has a longer half-life relative to recombinant human erythropoietin (rHuEPO), thus, allowing less frequent administration, increased convenience, and better compliance.

Methods: This retrospective analysis included 81 patients with MDS who were enrolled at 9 Spanish centers and who received once-weekly, subcutaneous DA (75-300 microg) for 16 weeks.

Results: Fifty-five percent of all patients (38 of 69 evaluable patients) achieved responses; 30.4% of were major responses, and 24.6% were minor responses; 64.7% of rHuEPO-naive patients and 45.7% rHuEPO-treated patients responded; and 43.2% had received previous rHuEPO. Most responses (65.8%) occurred at or before Week 8. The median age at diagnosis was 70 years (range, 38-87 years), the median age at the initiation of DA treatment was 75 years (range, 39-91 years), and 56.8% of patients were women. The median time from last ESP dose to DA initiation was 16.8 weeks (range, 0.0-159.0 weeks; <1 week in 53.1% of patients). According to the French-American-British classification system (n = 81 patients), 39.5% had refractory anemia (RA), 46.9% had RA with ringed sideroblasts, 9.9% had RA with excess blasts (RAEB), 1.2% had RAEB in transformation, and 2.5% had chronic myelomonocytic leukemia. According to the International Prognostic Scoring System (n = 47 patients), 55.3% of patients were in the low-risk group, and 36.2% of patients were in the intermediate-1-risk group. The median baseline hemoglobin level was 8.9 g/dL (range, 8.4-9.1 g/dL). The Starting DA dose was 75 microg per week in 3.7% of patients, 150 microg per week in 65.4% of patients, and 300 microg per week in 29.6% of patients (the dose was increased in 18.5% of patients and reduced in 9.9% of patients; median time to dose adjustment, 8 weeks). Five patients received granulocyte colony-stimulating factors. No DA-related adverse reactions occurred.

Conclusions: In the current study, 55% of evaluable patients with MDS safely achieved an erythroid response.